Trichomonas vaginalis is the cause of trichomoniasis, one of the most prevalent sexually transmitted infections. Despite the high occurrence of infection, little is understood about host-pathogen interactions. The overall goal of this study is to identify novel pathogenic factors involved in T. vaginalis infections. T. vaginalis-specific receptors on host cells have previously not been identified. The surfaces of Leishmania and T. vaginalis harbor similar phosphoglycans, and recently it has been found that the lymphocyte trafficking molecule dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN), is capable of binding to Leishmania. Aim 1 seeks to determine whether DC-SIGN on host cells may also be able to bind to T. vaginalis. New host-pathogen attachment factors will be identified in Aim 2. T. vaginalis mutants will be generated using transposon mutagenesis, screened by phenotypic assays, and genes responsible for the mutant phenotypes will be characterized. The effect of the parasite on the host immune response will also be analyzed. Aim 3 seeks to determine the cytokine and chemokine profile elicited by the host in response to T. vaginalis, and whether the parasite is capable of modulating the overall cytokine response via cysteine proteinases. In general, the results of these studies will greatly enhance our understanding of the pathogenesis of the parasite, which will ultimately lead to better treatment of the infection.